Design and introduction of quaternary ammonium hydroxide‐functionalized graphene oxide quantum dots as a pseudo-homogeneous catalyst for epoxidation of α,β-unsaturated ketones

In present work, design and synthesis of a novel pseudo-homogeneous catalyst is described. For this purpose, amine-functionalized graphene oxide quantum dots (N-GOQDs) were prepared from graphene oxide (GO) by a facile one-step oxidative fragmentation approach. The prepared N-GOQDs were then modified with quaternary ammonium hydroxide groups. Various characterization techniques clearly revealed that the quaternary ammonium hydroxide‐functionalized GOQDs (N-GOQDs/OH−) have been successfully synthesized. TEM image revealed that the GOQDs particles are almost regularly spherical in shape and mono-dispersed with particle sizes < 10 nm. The efficiency of the synthesized N-GOQDs/OH− as a pseudo-homogeneous catalyst in epoxidation of α,β-unsaturated ketones in the presence of aqueous H2O2 as an oxidant at room temperature was investigated. The corresponding epoxide products were obtained in good to high yields. This procedure has the advantages of a green oxidant, high yields, involvement of non-toxic reagents and reusability of the catalyst without discernible loss in activity.

www.nature.com/scientificreports/ various commercially available carbon sources including graphite powder, graphene oxide sheets, carbon fibers, citric acid, plant materials, such as mango leaves and so forth 6 .
Use of GOQDs as a support for active sites can be surprising since these catalytic systems allow the catalytic reaction occur under pseudo-homogeneous conditions. Therefore, the catalytically active species can be suspended indefinitely due to the small particle size of CQDs and designed functional groups on it, and catalyst and reactants are in a same phase, so the system can work similarly to a homogeneous catalyst with the added advantage of being recoverable effortlessly by dialysis membrane. Furthermore, the thin sheet of GOQDs contain a range of reactive oxygen functional groups on their surface, which provides high (aqueous) solubility and considerable potential for facile modification [10][11][12] . On the whole, surface modification techniques can offer exciting possibilities for change the surface of GOQDs for particular applications 13 . Recently, GOQDs supported catalysts have been explored in organic transformations and they demonstrated excellent results. Rezaei et al. were able to perform the selective oxidative cracking of alkenes to aldehydes using the carbon quantum dots supported ionic liquids 14 . Immobilized tungstate ions on the surface of carbon quantum dots have been successfully applied in oxidative scission of alkenes and selective oxidation of alcohols to corresponding aldehydes [15][16][17] . Pd and Ag nanoparticles have also stabilized on carbon quantum dots and the prepared catalyst was utilized as an efficient catalyst for promoting the Suzuki-Miyaura coupling reaction 18 .
Epoxides have emerged as an extremely useful class of organic compounds with high synthetic utility. In organic chemistry, epoxides are useful and versatile synthon so that can be converted into a wide variety of valuable compounds with good pharmaceutical profiles 19 . Epoxides compounds are also a broad family of monomers for production of various types of polymers. A number of epoxides derivatives have been reported to show anticancer, antibiotic and protease inhibition activities [20][21][22][23] . Therefore, academic researchers have been giving much concentration to preparation epoxides-containing compounds.
Epoxidation of carbon-carbon double bonds is one of the most fundamental reactions. This transformation has a wide scope of applications in synthetic organic chemistry 24,25 . Despite the large number of undesirable environmental and economic effects continue to use stoichiometric oxidations such as sodium peroxide, sodium hypochlorite, m-chloroperbenzoicacid, oxone, sodium chlorite, sodium perborate tetrahydrate, dimethyldioxirane, cyclohexylidenebishydroperoxide and trichloroisocyanuric acid [26][27][28][29][30][31][32][33][34] . During the recent decade, catalytic protocols based on aqueous hydrogen peroxide (H 2 O 2 ), air and pure oxygen as environmentally friendly, lowcost and readily available oxidants, are being considered 35 . Epoxidation of α,β-unsaturated ketones occurs in the presence of hydrogen peroxide under basic conditions and produces epoxy carbonyl compounds 36  . Although, great strides have been made in the development of affordable catalysts for the epoxidation of α,βunsaturated ketones approach focusing on the principles of green chemistry, however, it continues to be one of the most interesting areas in scientific literature.
As part of our continuing investigations to develop green catalysts for organic transformations and with the aim of further demonstrating the catalytic potential of GOQDs, on the first step of this study, N-GOQDs were prepared from graphene oxide by an oxidative fragmentation approach. Subsequently, the prepared N-GOQDs modified with quaternary ammonium hydroxide groups. The catalytic activity of this pseudo-homogeneous catalyst (N-GOQDs/OH -) was evaluated in the epoxidation of α,β-unsaturated ketones in the presence of aqueous H 2 O 2 as an oxidant at room temperature.

Experimental
Materials and apparatus. Used solvents and chemicals were supplied from Fluka (Switzerland) or Merck (Germany), and used without any further purification. Deionized (DI) water was applied in all tests. The Fourier-Transform Infrared Spectroscopy (FT-IR) spectra of the samples were recorded with the KBr pellet method by PerkinElmer PE-1600-FTIR spectrometer. Transmission electron microscopy (TEM) was investigated on an EM 208S (PHILIPS) 100 kV microscope with tungsten filament and Zeiss-EM10C (Germany) operating at 100 kV with samples on formvar carbon coated grid Cu mesh 300. The prepared samples were investigated by field emission scanning electron microscope (FESEM) (FESEM TESCAN MIRA 3, Czech). The 1 H NMR analysis was carried out with a BRUKER DRX-250 AVANCE spectrometer at 250.0 MHz. The optical characteristics of samples were measured by Shimadzu UV 2100 151PC UV-visible spectrophotometer at room temperature. Energy-dispersive X-ray spectroscopy (EDX) analysis were carried out on a SIGMA VP 500 (Zeiss) microscope equipped with an EDX measurement system. Synthesis of graphene oxide. First, the graphene oxide sheets have been prepared by the predominant modified Hummer's method. Briefly, concentrated H 2 SO 4 (15 mL) was added to a mixture of graphite (0.3 g) and NaNO 3 (0.3 g), and the mixture was cooled to 0 °C in an ice-salt bath. Under stirring, KMnO 4 (1.5 g) was added slowly to the suspension over 2 h at 0-10 °C with ice-salt bath cooling. The mixture was warmed to 35 °C and stirred for 30 min, and the resulting solution was diluted by slowly adding 30 mL of water under stirring. Then the reaction was stirred under reflux for 15 min at 98 °C. After cooling to room temperature, the resulting mixture was treated with 30% H 2 O 2 solution (7 mL). The mixture was washed with HCl and H 2 O respectively, followed by centrifugation and drying, graphene oxide was thus obtained (0.35 g) 44 . Synthesis of N-GOQDs. 0.02 g of as-prepared GO was dispersed in water (5 mL www.nature.com/scientificreports/ to room temperature and was centrifuged to remove the largest particles and untreated GO sheets. Ultimately, the dark yellow solution was dialyzed using a dialysis membrane (100 Da) to remove the unreacted starting materials, then concentrated under vacuum, giving final volume of 5 mL 45 . Synthesis of N-GOQDs/OH − . 5 mL methanol and 0.2 mL methyl iodide were added to 5 mL of N-GOQDs solution was. The mixture was stirred under reflux at 25 °C for 24 h. The product was then dialyzed using a dialysis membrane (100 Da) to remove the unreacted methyl iodide. Ultimately, 5 mL of quaternary ammonium iodide-functionalized N-GOQDs (N-GOQDs/I) was treated with 3 mL KOH (0.1 M) at room temperature for 2 h to obtain quaternary ammonium hydroxide-functionalized GOQDs (N-GOQDs/OH − ) 46 . Finally, the resulting solution was dialyzed using a dialysis membrane (100 Da) to remove any excess KOH, then was concentrated under vacuum to a final volume of 5 mL.
General procedure for epoxidation of α,β-unsaturated ketones using N-GOQDs/OH − . The catalysis experiments for the N-GOQDs/OH − was carried out in a 1,4-dioxane:water (1:1) mixture, using 1:3 α,β-unsaturated ketones:H 2 O 2 mole ratio. The α,β-unsaturated ketone (1 mmol) was introduced into a roundbottom flask equipped, to which N-GOQDs/OH − (4 mL of aqueous solution) and the mixture solvent (5 mL) were subsequently added. Then, aqueous 30% H 2 O 2 solution (3 mmol) was added, the reaction solution was stirred (at 1000 rpm) at ambient temperature for 24 h. After detecting the completion of the reaction using thinlayer chromatography (TLC) (n-hexane/ethyl acetate, 2/1), the reaction mixture was diluted with water (5 mL), and the product was extracted with ethyl acetate (3 × 5 mL). The extracted catalyst in the aqueous layer was concentrated under vacuum to a final volume of 4 mL to reuse in another run. On the other hand, the organic phase (ethyl acetate layer) containing unreacted α,β-unsaturated ketones and the corresponding epoxide products were evaporated and purified by employing a silica gel column chromatography (ethyl acetate/n-hexane) to obtain the desired products.

Results and discussion
Synthesis and characterization of the catalyst. GO has been synthesized using the modified Hummer's method. Hummer's method is an efficient and reliable method for producing GO through the oxidation of graphite powder with potassium permanganate in the presence of sodium nitrate in a solution of sulfuric acid 47 . Thereafter GO has been transformed into N-GOQDs by a "top-down" oxidative fragmentation route in the presence of aqueous H 2 O 2 and N-(aminomethyl)methanediamine ( Supplementary Fig. S1). Finally, N-GOQDs/ OH − has been prepared by converting the amine groups to quaternary methyl ammonium iodide followed by ion-exchange with aqueous KOH solution, as shown in Fig. 2. The presence of various functional groups on the surface of the N-GOQDs/OH − imparts high solubility in water and polar organic solvents, therefore, it can act as a pseudo-homogeneous catalyst. The as-synthesized GOQDs was characterized using Fourier transform infrared spectroscopy (FTIR), Energydispersive X-ray spectroscopy (EDX), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Fluorescence spectroscopy. Figure 1a shows FT-IR spectra of the prepared GO and N-GOQDs/OH − . GO shows its characteristic peaks at 3375, 1731, 1618, and 1044 cm −1 arising due to O-H, C=O, C=C and C-O-C of the epoxides, respectively. After the oxidative fragmentation, the carbonyl and epoxide peaks disappear (1731 and 1044 cm −1 respectively) 45 . The presence of -OH and -NH group in N-GOQDs/OH − was confirmed by the appearance of broad peak centered between 3000 cm −1 and 3500 cm −1 . The strong signal at 1668 cm −1 can be correspond to the stretching vibration of C=N and C=O bonds, and the peak at 1384 cm −1 arise due to stretching vibration of C and N bond 48 . The presence of aliphatic C-H group is confirmed by the peak at 2927 cm −1 . Therefore, the FT-IR image indicates that www.nature.com/scientificreports/ the compounds that contain nitrogen atoms are modified on the surface of the GOQDs. In the 1 H NMR spectrum, dispersed in D 2 O, the presence of quaternary ammonium hydroxide groups could be identified (Fig. 1b). Figure 2a,b shows TEM images of the obtained GO and the N-GOQDs/OH − and Fig. 2c shows the particle size distribution. The average the N-GOQDs/OH − size must be significantly smaller than the GO. The TEM images (Fig. 2b) clearly reveal the N-GOQDs/OH − are nearly spherical in shape and mono-dispersed with particle sizes smaller than 10 nm whose mean size is very smaller than GO (Fig. 2a). Figures 2d,e show SEM images of the prepared GO and N-GOQDs/OH − , respectively. According to the FE-SEM image (Fig. 2e) of the GOQDs show sphere-shaped morphology.
To study the distribution and chemical composition of the N-GOQDs/OH − , EDX analysis was performed ( Supplementary Fig. S2). A SEM image of the same region as the EDX is shown in Supplementary Fig. S2a. The elemental peaks attributed to carbon, oxygen, and nitrogen in the EDX spectrum confirmed the presence of these elements in the obtained N-GOQDs/OH − (Supplementary Fig. S2b). Additionally, the EDX spectrum reveals the presence of an ignorable amount of potassium and calcium impurities (0.05 and 0.10 atom percent, respectively) (Supplementary Table S1). The presence of potassium can be related to an extremely small amount of KOH not removed in the dialysis step and the presence of calcium is a sign of environmental impurity in the catalyst identification stage. Therefore, the EDX spectrum confirmed good anchoring and stability of compounds that contain nitrogen atoms on GOQDs. Additionally, it can be inferred from the mapping images that elements of carbon, oxygen, and nitrogen are widespread in the area of N-GOQDs/OH − because of the uniform formation of N-GOQDs/OH − (Supplementary Fig. S2c).
Fluorescence spectroscopy is a simple and reliable methodology to confirm the quantum confined properties of semiconductor QDs 45,49 . The fluorescence response of the N-GOQDs/OH − with regard to a variety of excitation wavelengths between 320 and 540 nm is displayed in Fig. 3. Consistent with previous research, the fluorescence intensity of the N-GOQDs/OH − sample first increased and then decreased (Fig. 3). The samples displayed exhibited the strongest fluorescence peak with maximum emission centered at 445 nm at an excitation wavelength of 360 nm. The results clearly indicated the successful synthesis of the N-GOQDs/OH − samples. Furthermore, photographs of an aqueous dispersion of N-GOQDs/OH − under room light (left) and under 365 nm UV irradiation (right) shown in the figure.
The atomic chemical states of synthesized N-GOQDs/OH − sample was studied by XPS (Fig. 4). The full XPS spectra of N-GOQDs/OH − clearly reveals the existence of carbon, oxygen and nitrogen (Supplementary Fig. S3). www.nature.com/scientificreports/ C1s spectrum shows peaks at BEs of 284 eV (referring to C-C and C=C), 286 eV (referring to C-O and C-N) and 288 eV (referring to C=O) (Fig. 4). The analysis of O1s shows peaks at BEs of 530 eV (assigned to C-O and C=O), and 532 eV (assigned to O-H) (Fig. 4). The N1s shows peaks at 400 eV and 402 eV corresponding to C-N and the quaternary ammonium group, respectively (Fig. 4)  Investigation of catalytic activity of N-GOQDs/OH − in epoxidation of α,β-unsaturated ketones. The catalytic activity of N-GOQDs/OH − , as a pseudo-homogeneous catalyst, was evaluated in epoxidation of α,β-unsaturated ketones. Initially, the epoxidation of benzalacetophenone was studied as standard substrate with the prepared nanocatalyst (Table 1). At the outset, many experimental parameters, such as catalyst amount, the H 2 O 2 /α,β-unsaturated ketones molar ratios and solvent have been studied in order to determine the optimal experimental conditions. The effect of reaction conditions on epoxidation of benzalacetophenone (1 mmol) with N-GOQDs/OH − summarized in Table 1. As can be seen from the results in Table 1, in the absence of the catalyst, and in the presence of GO or N-GOQDs, no product obtained (Table 1, Entries 1-3) and an increase in the amount of the catalyst improve the yields significantly ( Table 2, Entries 4-6). The effect of addition of H 2 O 2 amount on the reaction was also studied. The yield significant improvements of epoxide product were observed with increasing amount of H 2 O 2 (Entries 6-10). Investigating the role of solvent show that the   Table 2. The present procedure is general as a wide range of α,β-unsaturated ketones derivatives with electron-donating and electron-withdrawing groups reacted easily with H 2 O 2 at room temperature to afford the corresponding α,β-epoxy ketones in good to high yields and electronic effect of the substituents was not observed.
According to the literature, plausible mechanisms for the epoxidation of α,β-unsaturated ketones is proposed as shown in Fig. 5. The OH − plays an essential role through formed HOO − specie. On the other hand, the N-GOQDs/OH − activate the α,β-unsaturated ketones through hydrogen-bond interaction. The reaction is followed by the nucleophile attack of the HOO − and form a hydroperoxide enolate. Finally, the reaction is completed by lost the OHand formed the epoxide ring [53][54][55][56] .
After completion of the reaction in a homogeneous system, the reaction mixture was diluted with water, and the product was extracted with ethyl acetate. Since the catalyst is completely soluble in water, the catalyst was retained in the aqueous phase. The extracted catalyst in the aqueous layer was concentrated under vacuum to a final volume of 4 mL to reuse in another run. Recycling experiments confirmed the acceptable reusability and chemical stability of the catalyst since the recovered catalyst can be used during four runs (Fig. 6). Table 3 lists the comparison of catalytic performance of N-GOQDs/OH − as a pseudo-homogeneous catalyst for the epoxidation of benzalacetophenone with various reported catalysts. Compared with some data in the literature, the N-GOQDs/OH − revealed appropriate catalytic performance and good reusability for the epoxidation of benzalacetophenone.

Conclusion
In summary, quaternary ammonium hydroxide-functionalized GOQDs has been prepared. The provided GOQDs were characterized using 1 H NMR, FT-IR, TEM, SEM, XPS, EDX mapping, and fluorescence spectroscopy. On the whole, results of these analysis support the expected structure of N-GOQDs/OH − . The catalyst was found to be active towards epoxidation of α,β-unsaturated ketones in the presence of aqueous H 2 O 2 as a green oxidant, at ambient temperature. The corresponding epoxide products were obtained in good to high yields. Due to the presence of various functional groups on the surface of the N-GOQDs/OH − imparts high solubility in water and polar organic solvents. Therefore substrates and the catalyst can create a homogeneous phase, this helps to achieve a high efficiency of the catalyst. This pseudo-homogeneous catalyst will be widely expected to use for future catalytic applications in oxidation reactions of organic compounds. www.nature.com/scientificreports/  Figure 5. The plausible mechanism for the epoxidation reaction.